lisW-S

lisW-S (lisinopril-tryptophan) is a novel, highly selective small molecule inhibitor of the C-domain of the somatic angiotensin-converting enzyme (ACE). Somatic ACE consists of two homologous catalytic domains, the N- and C-domains, which have different substrate specificities. While traditional ACE inhibitors like lisinopril non-selectively block both domains, lisW-S is designed to specifically target the C-domain, which is more efficient at converting angiotensin I to the potent vasoconstrictor angiotensin II. This domain selectivity is intended to maintain antihypertensive efficacy while potentially avoiding side effects such as cough and angioedema, which are associated with N-domain inhibition and the subsequent accumulation of bradykinin. Preclinical studies in rat and mouse models of hypertension and myocardial infarction have demonstrated that lisW-S effectively reduces blood pressure and renal angiotensin II levels without significantly increasing plasma bradykinin levels or affecting N-domain-specific substrates like Ac-SDKP.

Other names

lisinopril-tryptophan